Human monoclonal antibodies with specificity for human malignancies will be important biological agents, both to investigate the nature of the human immune response to neoplastic disease and for diagnostic and therapeutic purposes. The two key elements necessary for success in this field are: 1) development of sensitized lymphocytes antibodies to tumor-associated antigens; and 2) development of adequate human myeloma cell lines for fusion. In collaboration with the Lymphokines Section, LMI, this laboratory has developed a model for in vitro sensitization of human peripheral blood lymphocytes and subsequent fusion to a human myeloma cell line to produce antigen-specific human monoclonal antibodies. This laboratory has also determined the optimal human myeloma cell lines for construction of human hybridomas secreting antibodies. Current projects involve sensitization of lymphocytes with melanoma-associated antigen (250K) which has proved successful and then fusion of these lymphocytes with a human myeloma cell line.